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https://www.readbyqxmd.com/read/29150289/the-cause-of-multiple-sclerosis-is-autoimmune-attack-of-adenosyltransferase-thereby-limiting-adenosylcobalamin-production
#1
J L Boucher
The pathogenesis of multiple sclerosis (MS) begins with an infection by a bacterium from the class of bacteria that produce and utilize adenosylcobalamin (AdoCbl) and possess an adenosyl transferase enzyme (ATR); these bacteria are the exogenous antigens that cause MS. Human ATR is homologous to bacterial ATR and B cells produce anti-ATR antibodies as an autoimmune response thereby reducing the concentration of ATR and thus limiting production of AdoCbl, one of the two bioactive forms of vitamin B12. The next step in MS pathogenesis is a period of subclinical AdoCbl deficiency over a period of many years resulting in production of odd-carbon-number fatty acids that are incorporated into myelin rendering it antigenic...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29149383/diffusion-mri-in-pediatric-brain-injury
#2
Emily L Dennis, Talin Babikian, Christopher C Giza, Paul M Thompson, Robert F Asarnow
Traumatic brain injury (TBI) is a major public health issue around the world and can be especially devastating in children as TBI can derail cognitive and social development. White matter (WM) is particularly vulnerable to disruption post-TBI, as myelination is ongoing during this period. Diffusion magnetic resonance imaging (dMRI) is a versatile modality for identifying and quantifying WM disruption and can detect diffuse axonal injury (DAI or TAI (traumatic axonal injury)). This review covers dMRI studies of pediatric TBI, including mild to severe injuries, and covering all periods post-injury...
October 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29148104/neuregulin-1-promotes-remyelination-and-fosters-a-pro-regenerative-inflammatory-response-in-focal-demyelinating-lesions-of-the-spinal-cord
#3
Hardeep Kataria, Arsalan Alizadeh, Ghazaleh M Shahriary, Shekoofeh Saboktakin Rizi, Ryan Henrie, Kallivalappil T Santhosh, James A Thliveris, Soheila Karimi-Abdolrezaee
Oligodendroglial cell death and demyelination are hallmarks of neurotrauma and multiple sclerosis that cause axonal damage and functional impairments. Remyelination remains a challenge as the ability of endogenous precursor cells for oligodendrocyte replacement is hindered in the unfavorable milieu of demyelinating conditions. Here, in a rat model of lysolecithin lysophosphatidyl-choline (LPC)-induced focal demyelination, we report that Neuregulin-1 (Nrg-1), an important factor for oligodendrocytes and myelination, is dysregulated in demyelinating lesions and its bio-availability can promote oligodendrogenesis and remyelination...
November 17, 2017: Glia
https://www.readbyqxmd.com/read/29146475/electrical-activity-of-sensory-pathways-in-female-and-male-geriatric-rhesus-monkeys-macaca-mulatta-and-its-relation-to-oxidative-stress
#4
A Ibáñez-Contreras, U Hernández-Arciga, A Poblano, M Arteaga-Silva, B Hernández-Godínez, G I Mendoza-Cuevas, R Toledo-Pérez, A Alarcón-Aguilar, V Y González-Puertos, M Konigsberg
Synapses loss during aging has been related to decreased neuronal excitability and reduced electrophysiological activity in the nervous system, as well as to increased brain damage. Those physiological and biochemical alterations have been related to the oxidative stress increase associated with old age. The main substrate of lipid peroxidation (LPX) in the central and peripheral nervous systems are the myelin sheaths, and their damage generates a delayed nerve conduction velocity. However, studies in which the neural conduction velocity is related to changes in the redox state are still lacking...
November 13, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29143589/biomarkers-in-the-evolution-of-multiple-sclerosis
#5
Thomas Berger
Nonimaging biomarkers can be applied in differential diagnosis, evaluation of disease progression and therapy monitoring of multiple sclerosis (MS). Presence of oligoclonal IgG bands in cerebrospinal fluid is a diagnostic element and a negative predictor of MS evolution. AQP4 antibodies are pathogenic and diagnostic for neuromyelitis optica spectrum disorder. Antibodies to myelin oligodendrocyte glycoprotein develop in about 50% of predominantly pediatric patients with acute disseminated encephalomyelitis, but their possible role in pathogenesis is unknown...
November 2017: Neurodegenerative Disease Management
https://www.readbyqxmd.com/read/29143164/upregulation-of-myelin-gene-expression-by-a-physically-modified-saline-via-phosphatidylinositol-3-kinase-mediated-activation-of-creb-implications-for-multiple-sclerosis
#6
Malabendu Jana, Supurna Ghosh, Kalipada Pahan
An increase in central nervous system (CNS) remyelination and a decrease in CNS inflammation are important steps to halt the progression of multiple sclerosis (MS). RNS60 is a bioactive aqueous solution generated by subjecting normal saline to Taylor-Couette-Poiseuille flow under elevated oxygen pressure. Recently we have demonstrated that RNS60 exhibits anti-inflammatory properties. Here, we describe promyelinating property of RNS60. RNS60, but not normal saline (NS), RNS10.3 (TCP-modified saline without excess oxygen) or PNS60 (saline containing excess oxygen without TCP modification), stimulated the expression of myelin-specific genes and proteins (myelin basic protein, MBP; myelin oligodendrocyte glycoprotein, MOG and proteolipid protein, PLP) in primary mouse oligodendroglia and mixed glial cells...
November 15, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29142736/strain-differences-in-cuprizone-induced-demyelination
#7
Qili Yu, Ryan Hui, Jiyoung Park, Yangyang Huang, Alexander W Kusnecov, Cheryl F Dreyfus, Renping Zhou
Background: Multiple sclerosis (MS) is a severe neurological disorder, characterized by demyelination of the central nervous system (CNS), and with a prevalence of greater than 2 million people worldwide. In terms of research in MS pathology, the cuprizone toxicity model is widely used. Here we investigated the contribution of genetic differences in response to cuprizone-induced demyelination in two genetically different mouse strains: CD1 and C57BL/6. Results: We demonstrate that exposure to a diet containing 0...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29142295/regenerating-cns-myelin-from-mechanisms-to-experimental-medicines
#8
REVIEW
Robin J M Franklin, Charles Ffrench-Constant
Although the core concept of remyelination - based on the activation, migration, proliferation and differentiation of CNS progenitors - has not changed over the past 20 years, our understanding of the detailed mechanisms that underlie this process has developed considerably. We can now decorate the central events of remyelination with a host of pathways, molecules, mediators and cells, revealing a complex and precisely orchestrated process. These advances have led to recent drug-based and cell-based clinical trials for myelin diseases and have opened up hitherto unrecognized opportunities for drug-based approaches to therapeutically enhance remyelination...
November 16, 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/29142145/clinical-course-therapeutic-responses-and-outcomes-in-relapsing-mog-antibody-associated-demyelination
#9
Sudarshini Ramanathan, Shekeeb Mohammad, Esther Tantsis, Tina Kim Nguyen, Vera Merheb, Victor S C Fung, Owen Bruce White, Simon Broadley, Jeannette Lechner-Scott, Steve Vucic, Andrew P D Henderson, Michael Harry Barnett, Stephen W Reddel, Fabienne Brilot, Russell C Dale
OBJECTIVE: We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination. METHODS: We evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients. RESULTS: The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children...
November 15, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29141977/vitamins-associated-with-brain-aging-mild-cognitive-impairment-and-alzheimer-disease-biomarkers-epidemiological-and-experimental-evidence-plausible-mechanisms-and-knowledge-gaps
#10
REVIEW
Michael Fenech
The key to preventing brain aging, mild cognitive impairment (MCI), and Alzheimer disease (AD) via vitamin intake is first to understand molecular mechanisms, then to deduce relevant biomarkers, and subsequently to test the level of evidence for the impact of vitamins in the relevant pathways and their modulation of dementia risk. This narrative review infers information on mechanisms from gene and metabolic defects associated with MCI and AD, and assesses the role of vitamins using recent results from animal and human studies...
November 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/29141799/the-4259a-c-polymorphism-of-tim-3-but-not-1637c-t-polymorphism-of-tim-1-is-associated-with-multiple-sclerosis-in-isfahan-population
#11
Masoumeh Pouladian, Mazdak Ganjalikhani-Hakemi, Fereshteh Alsahebfosul, Vida Homayouni, Sharifeh Khosravi, Masoud Etemadifar, Fariba Mazrouei, Rasoul Salehi
BACKGROUND: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) which initiated and mediated by autoreactive T helper1 cells directed against myelin antigens. One of T cell surface receptors is T cell immunoglobulin and mucin domain (TIM) family which its importance in immunology is recently discovered. These molecules have important immunological function by regulation of T effector cells. METHODS: In the present study, we analyzed the frequency of +4259A>C polymorphism in TIM-3 and -1637C>T polymorphism in TIM-1 gene in MS patients and healthy controls using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29141790/cerebral-toxoplasmosis-in-an-ms-patient-receiving-fingolimod
#12
Alejandro Enriquez-Marulanda, Jaime Valderrama-Chaparro, Laura Parrado, Juan Diego Vélez, Ana Maria Granados, Jorge Luis Orozco, Jairo Quiñones
Multiple Sclerosis (MS) is an autoimmune disease in which lymphocytes target putative myelin antigens in the CNS, causing inflammation and neurodegeneration. Fingolimod (FTY720) is an immunosuppressive drug used as a second line therapy for relapsing forms of MS due to its safety profile and good response to treatment. Despite its safety, there are still concerns about the possibility of Fingolimod being linked to the development of opportunistic infections like disseminated varicella zoster infections and herpes simplex encephalitis...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29141529/experimental-autoimmune-encephalomyelitis-eae-model-of-cynomolgus-macaques-induced-by-recombinant-human-mog1-125-rhmog1-125-protein-and-mog34-56-peptide
#13
Yunxiao Sun, Zhen Peng, Libiao Zhang, Huaqian Wang, Xiangyang He, Xingwen Peng, Qin Zhang, Hui Liu, Junhua Rao, Haifeng Wang, Jie Wu
Experimental autoimmune encephalomyelitis (EAE) induced by self-myelin antigen is a widely used multiple sclerosis (MS) model for preclinical studies of new therapeutics and potential pathogenesis. By comparison with rodent EAE models, EAE models in primates are more similar to MS. Some groups have developed EAE models in primates by using common marmoset (Callithrix jacchus). However, this model has some limitations. EAE in cynomolgus monkey (Macaque fasciculrais) could overcome these limitations. In this study, EAE was induced in cynomolgus monkey by immunizing with the recombinant human myelin oligodendrocyte glycoprotein extracellular domain (1-125) (rhMOG1-125) and a synthetic peptide, representing peptide 34-56 of human myelin oligodendrocyte glycoprotein (MOG34-56) in complete Freund's adjuvant (CFA) and in combination with intravenous injection of pertussis toxin, and subsequent booster immunizations with the same dose of antigen in incomplete Freund's adjuvant (IFA) until the animals developed clinically significant EAE (score≥2)...
November 9, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/29141393/-the-role-of-myelin-oligodendrocyte-glycoprotein-antibodies-for-detection-of-demyelinating-optic-neuritis
#14
S H Wei, Y Zhao
The incidence of neuromyelitis optica spectrum disorders (NMOSD) in the Asian population is much higher than in Europe and North America. Optic neuritis is the first sign of NMOSD for some people. Identification of aquaporin 4 antibody is a milestone in the research of NMOSD and has been included in the diagnosis standard of NMOSD, but about 20% to 30% of NMOSD patients is aquaporin 4 antibody-negative. With the cell-based assays, oligodendrocyte glycoprotein antibodies in demyelinating diseases of the central nervous system have aroused the attention of researchers...
November 11, 2017: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
https://www.readbyqxmd.com/read/29140922/fingolimod-reduces-neuropathic-pain-behaviors-in-a-mouse-model-of-multiple-sclerosis-by-a-sphingosine-1-phosphate-receptor-1-dependent-inhibition-of-central-sensitization-in-the-dorsal-horn
#15
Suzanne Doolen, Tommaso Iannitti, Benjamin C Shaw, Carolyn M Grachen, Renee R Donahue, Bradley K Taylor
Multiple sclerosis (MS) is an autoimmune-inflammatory neurodegenerative disease that is often accompanied by a debilitating neuropathic pain. Disease-modifying agents slow the progression of MS and prevent relapses, yet it remains unclear if they yield analgesia. We explored the analgesic potential of fingolimod (FTY720), an agonist/functional antagonist at the sphingosine-1-phosphate receptor 1 (S1PR1), because it reduces hyperalgesia in models of peripheral inflammatory and neuropathic pain. We used a myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) mouse model of experimental autoimmune encephalomyelitis (EAE), modified to avoid frank paralysis and thus allow for assessment of withdrawal behaviors to somatosensory stimuli...
November 13, 2017: Pain
https://www.readbyqxmd.com/read/29137918/spinobulbar-muscular-atrophy-combined-with-atypical-hereditary-neuropathy-with-liability-to-pressure-palsy
#16
Kyomin Choi, So Hyun Ahn, Seol-Hee Baek, Jun-Soon Kim, Seok-Jin Choi, Je-Young Shin, Sung-Min Kim, Yoon-Ho Hong, Jung-Joon Sung
Spinobulbar muscular atrophy (SBMA) is an X-linked recessive disease, presenting motor weakness and wasting of facial, bulbar and limb muscles. Hereditary neuropathy with liability to pressure palsy (HNPP) is autosomal dominant disorder characterized by recurrent neuropathies at common entrapment sites. We report a case of co-existence of SBMA and atypical HNPP with genetic confirmation of CAG expansion in the androgen receptor (AR) gene and deletion of the peripheral myelin protein 22 (PMP22) gene. A 62-year-old man presented with progressive muscle weakness, fasciculations in upper and lower limbs and dysesthesia predominantly in the distal regions...
November 11, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29137569/the-neuro-ophthalmological-effects-related-to-long-term-occupational-exposure-to-organic-solvents-in-painters
#17
Heba Khodary Allam, Shaimaa Soliman, Tamer Wasfy, Ahmed Ghoneim, Yasser Serag, Grace Simbajwe
PURPOSE: Organic solvents are widely used in many industries, and usually, exposure occurs with mixtures of solvents. Organic solvent mixtures are known for their ability to affect tissues of high lipid content including the myelin sheath in the nervous system. The purpose of this work was to study the evidence that long-term (more than 10 years) exposure to organic solvent mixtures among painters can induce neuro-ophthalmological effects on the function of retinal ganglion cells and the optic tract...
January 1, 2017: Toxicology and Industrial Health
https://www.readbyqxmd.com/read/29137252/a-novel-mutation-r190h-in-the-at-hook-1-domain-of-mecp2-identified-in-an-atypical-rett-syndrome
#18
Xiao Zhou, Yuangao Liao, Miaojing Xu, Zhong Ji, Yunqi Xu, Liang Zhou, Xiaoming Wei, Peiqian Hu, Peng Han, Fanghan Yang, Suyue Pan, Yafang Hu
Background: Mutations in Methyl-CpG binding protein 2 (MECP2) have been identified as the disease-causing mutations in Rett Syndrome (RTT). However, no mutation in the AT-hook 1 domain of MECP2 has been reported in RTT yet. The function of AT-hook 1 domain of MECP2 has not been described either. Methods: The clinical and radiological features of a girl with progressive hyperactivity and loss of acquired linguistic and motor functions were presented. Next generation sequencing was used to screen the causative gene...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136549/the-spectrum-of-charcot-marie-tooth-disease-due-to-myelin-protein-zero-an-electrodiagnostic-nerve-ultrasound-and-histological-study
#19
Gian Maria Fabrizi, Stefano Tamburin, Tiziana Cavallaro, Ilaria Cabrini, Moreno Ferrarini, Federica Taioli, Francesca Magrinelli, Giampietro Zanette
OBJECTIVE: Nerve ultrasound (US) data on myelin protein zero (MPZ)-related Charcot-Marie-Tooth disease (CMT) are lacking. To offer a comprehensive perspective on MPZ-related CMTs, we combined nerve US with clinics, electrodiagnosis and histopathology. METHODS: We recruited 36 patients (12 MPZ mutations), and correlated nerve US to clinical, electrodiagnostic measures, and sural nerve biopsy. RESULTS: According to motor nerve conduction velocity (MNCV) criteria, nine patients were categorized as "demyelinating" CMT1B, 17 as "axonal" CMT2I/J, and 10 as dominant "intermediate" CMTDID...
October 20, 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/29134703/origin-and-dynamics-of-oligodendrocytes-in-the-developing-brain-implications-for-perinatal-white-matter-injury
#20
REVIEW
Erik van Tilborg, Caroline G M de Theije, Maurik van Hal, Nienke Wagenaar, Linda S de Vries, Manon J Benders, David H Rowitch, Cora H Nijboer
Infants born prematurely are at high risk to develop white matter injury (WMI), due to exposure to hypoxic and/or inflammatory insults. Such perinatal insults negatively impact the maturation of oligodendrocytes (OLs), thereby causing deficits in myelination. To elucidate the precise pathophysiology underlying perinatal WMI, it is essential to fully understand the cellular mechanisms contributing to healthy/normal white matter development. OLs are responsible for myelination of axons. During brain development, OLs are generally derived from neuroepithelial zones, where neural stem cells committed to the OL lineage differentiate into OL precursor cells (OPCs)...
November 14, 2017: Glia
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